G. HUMAN SUBJECTS This section has been prepared by Marc Schuckit, Chairman of the COGA Ethics Subcommittee. It updates, in detail, several issues that are directly pertinent to COGA as a family and genetic research study and that are applicable to all 6 subject collection sites (SUNY HSC at Brooklyn, University of Connecticut, Indiana University, University of lowa, University of California, San Diego, Washington University). The Human Studies Committee/Institutional Review Board (IRB) at each COGA site has supervised the work since the inception of COGA, including reviews in the past 12 months, and will review this current proposal, the consent forms, and the various recruitment letters. We also focus on incorporating HIP/\A guidelines as described below. 1. An Overview of Subject Selection and Characteristics The original COGA Guidelines for selection of probands, Identiflcation of appropriate relatives, and selection of controls and their families are outiined above. The proposed work will recruit no new families and will only draw upon members of the existing pedigrees. Appropriate members of COGA probands and comparison families will be invited to continue to participate In the prospective panel study, along with children who "age up" to the 12-year minimum age required for participation. Alcoholic probands had been originally ascertained from consecutive admissions to public and private inpatient and outpatient treatment facilities at each ofthe COGA participating sites. This Included individuals who fulfilled the COGA criteria for alcohol dependence, and who had multiple alcohol-dependent relatives living within 50 to 150 miles ofthe COGA Centers. Comparison families were selected using different methods across the subject collection sites, with approaches including random mailings to individuals affiliated with the respective university, people who are attending dental and medical clinic patients, and a random assessment through public records. Potential probands were excluded from the study if they had a mortal illness, were current IV drug users, reported an extensive history of IV drug use (31+ times), or were known to be infected with the HIV virus. These exclusion criteria are not applied to family members. In general, for all subjects medical or psychiatric conditions were the only general grounds for exclusion if it seemed probable that they might compromise a subject's ability to provide informed consent (e.g., advanced Alzheimer's disease) or hinder one's participation in the blood sampling or electrophysiological portions ofthe study (e.g., liver disease, neurological disease, head injuries, etc.). For the current ongoing study of adolescents and young adults, individuals younger than the age of majority (18 years) are assessed (including direct interviews, neurophysiological and electrophysiological testing, and blood samples) only following written consent is obtained from the parents and assent of the subject. The study of adolescents and young adults is essential to facilitate genetic analyses of characteristics related to the onset of alcohol and substance use and associated problems. These findings will facilitate our understanding of the potential importance of specific genetic markers and enhance our understanding of eariy drinking parameters.